Cardiol J. 2021 Oct 13. doi: 10.5603/CJ.a2021.0122
Luiza Szarpak 1 2, Krzysztof J Filipiak 3, Aleksandra Gasecka 4 5, Wladyslaw Gawel 2 6, Dorota Koziel 7, Milosz J Jaguszewski 8, Jaroslaw Chmielewski 9, Anatolii Gozhenko 10, Karol Bielski 2 11, Pawel Wroblewski 12, Ivan Savytskyi 10, Lukasz Szarpak 13 14, Zubaid Rafique 15
- COVID-19 risk reduced by vitamin D supplementation – umbrella review of 7 meta-analysis – Oct 2021
- COVID-19 treated by Vitamin D (example: ICU reduced by 5X) – 20th meta-analysis Oct 13, 2021
- Severe COVID-19 2.5 X more likely if low vitamin D (23 studies) – 19th meta-analysis Oct 2021
- COVID-19 mortality extrapolates to zero at 50 ng of vitamin D – 18th Meta-analysis Sept 2021
- COVID-19 death 1.6 X more likely if low vitamin D (24 studies) – 17th meta-analysis Aug 2021
- Severe COVID-19 5X more likely if low vitamin D (23 studies) – 16th meta-analysis July 2021
- Severe COVID-19 3.5 more likely if low vitamin D (30 studies) – meta-analysis July 2021
- COVID-19 patients who had supplemented with Vitamin D were 3X less likely to enter ICU – June 2021
- Low Calcium associated with severe COVID-19 – several studies
- COVID-19 mortality 3X more likely if low vitamin D (999,179 people) – meta-analysis March 29, 2021
- COVID-19 was 2.6X more severe if very low Vitamin D (43 studies) – meta-analysis March 26, 2021
- Low Vitamin D associated with 2.7X more severe COVID-19 – 12th MA March 5, 2021
- Vitamin D supplementation fights COVID-19 – 11th meta-analysis Jan 24, 2021
- 3.7 X less likely to die of COVID-19 if supplemented with Vitamin D - meta-analysis Jan 5, 2021
- Less likely to test positive for COVID-19 if higher Vitamin D – meta-analysis Jan 6, 2021
- Vitamin D reduces COVID-19 by 80 percent - anonymous meta-analysis - Jan 5, 2021
- COVID-19 1.7X more likely to be severe if low Vitamin D - meta-analysis Oct 2020
- Low Vitamin D associated 1.8X increased risk of COVID-19 death in hospital – meta-analysis Nov 4, 2020
- Acute viral respiratory infections (RTI) reduced by Vitamin D - 20 reviews - Aug 2020
- Prudent to consider that Vitamin D has a role in COVID-19 – meta-analysis – Aug 7, 2020
- Risk of enveloped virus infection is increased 50 percent if poor Vitamin D Receptor - meta-analysis Dec 2018
- Hepatitis B patients have 2 ng lower level of Vitamin D – meta-analysis June 2019
- Influenza Vaccination not benefited by lowish levels of vitamin D – meta-analysis March 2018
- As of Dec 2, 2021, the VitaminDWiki page had: 34 trials, 6 trial results, 28 meta-analyses and reviews, 64 observations, 36 recommendations, 55 associations, 89 speculations, 52 videos see related: Governments, HealthProblems, Hospitals, Dark Skins, 26 risk factors are ALL associated with low Vit D, Recent Virus pages Fight COVID-19 with 50K Vit D weekly Vaccines
Background: Vitamin D is a likely candidate for treatment as its immune modulating characteristics have effects on coronavirus disease 2019 (COVID-19) patients. It was sought herein, to summarize the studies published to date regarding the vitamin D supplementation to treat severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive patients.
Methods: A systematic review and meta-analysis were performed following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The primary outcome were 14-day and in-hospital mortality reported as an odds ratio (OR) with the associated 95% confidence interval (CI).
Results: Eight articles were included in the review with a combined total of 2,322 individual patients, 786 in the vitamin D supplementation group and 1,536 in the control group. The use of vitamin D compared to the group without vitamin D supplementation was associated with a
- lower 14-day mortality (18.8% vs. 31.3%, respectively; OR = 0.51; 95% CI: 0.12-2.19; p = 0.36), a
- lower in-hospital mortality (5.6% vs. 16.1%; OR = 0.56; 95% CI: 0.23-1.37; I² = 74%; p = 0.20), the
- rarer intensive care unit admission (6.4% vs. 23.4%; OR = 0.19; 95% CI: 0.06-0.54; I² = 77%; p = 0.002) as well as
- rarer mechanical ventilation (6.5% vs. 18.9%; OR = 0.36; 95% CI: 0.16-0.80; I² = 0.48; p = 0.01).
Conclusions: Vitamin D supplementation in SARS-CoV-2 positive patients has the potential to positively impact patients with both mild and severe symptoms. As several high-quality randomized control studies have demonstrated a benefit in hospital mortality, vitamin D should be considered a supplemental therapy of strong interest. Should vitamin D prove to reduce hospitalization rates and symptoms outside of the hospital setting, the cost and benefit to global pandemic mitigation efforts would be substantial.
Though global vaccination against the SARS-CoV-2 virus has been ongoing since late 2020 and the various vaccines continue to be effective at preventing hospitalizations , more infectious variants of SARS-CoV-2 are fueling a rebound in infections among the unvaccinated . As most countries will not achieve herd immunity from vaccination efforts until well into 2022, COVID-19 will likely continue to occupy hospital systems in countries all over the world . Treatment for hospitalized COVID-19 patients will also limit access to essential medical services for people suffering from chronic and degenerative diseases .
As a consequence, research into potential therapeutic agents such as azithromycin and chloroquine have made headlines [29, 30], however these strategies proved futile and even dangerous [31, 32]. Additionally, the use of Lopinavir, Ritonavir, Remdesivir, Oseltamivir, Ribavirin to treat COVID-19 also proved not to be effective [33, 34].
At this time, vitamin D, which has immunomodulating characteristics and has been shown to be associated with better outcomes in upper respiratory tract infections, should be a candidate of interest in mitigating COVID-19 [35, 36]. This inexpensive and readily available supplement could be rapidly and widely implemented with minimal risk of detriment to the general public. The implementation of which could result in decreased ICU admissions that could reduce the number of occupied ICU beds and result in better clinical outcomes . In one randomized control ICU study, supplemental vitamin D administered to COVID-19 patients, alongside existing therapy, was associated with lower ICU admission and mortality . The inclusion criteria included COVID positive patients with clinical and radiological findings of ARDS and resulted in a reduction in ICU treatment and a reduction of symptoms.
It must be noted that the groups did not differ at the baseline with the control group presenting more often with hypertension while the clinical group was slightly older .
It has been hypothesized that the benefits of vitamin D in patients suffering from ARDS are due to the activation of the vitamin D receptor (VDR) pathway, resulting in a decrease of cytokine expression , a central cause of rapid deterioration . Additionally, vitamin D deficiency in ICU patients is common  and may indicate that other complications in COVID-19 infections are the result of this deficiency . When a combination of vitamin D/magnesium/vitamin B12 were administered the older patients, this combination was found to reduce the need for the more advanced procedures without adding significant costs . The rationale for this combination lies in the fact that magnesium enhances vitamin D activity and plays a pivotal role in the immune system [41, 42]. Additionally, vitamin B12 stabilizes the gut microbiota, which has also played a pivotal role in a patient’s overall health [43, 44]. These observations are reinforced by other studies where vitamin D administered in frail elderly patients was associated with better survival rate and less severe COVID-19 course .
However, other studies have found that the administration of vitamin D in COVID-19 patients conveyed no clinical benefit in terms of severity of disease, while also being associated with a twofold increase in mortality rate . It can be hypothesized that late administration of vitamin D in the presence of severe inflammation could impair the metabolism of vitamin D , resulting in a buildup of the metabolites.
The last study included in this review found that the administration of vitamin D administration had no effect on the severity of the course of COVID-19 infections . It should be noted that the protocol of this trial included the administration of a onetime dose of 200,000 IU of vitamin D among hospitalized patients with moderate or severe disease. It is not clear if this one dose regiment is sufficient as many patients with upper respiratory tract conditions display, e.g., asthma, impaired function of the CYP2R1 (vitamin D 25-hydroxylase)  which is an enzyme that catalyzes the formation of vitamin D3 to 25-hydroxyvitamin D3 (25(OH)D3), which reduces the biologically active form of vitamin D.
- da Silva FC, Barbosa CP. The impact of the COVID-19 pandemic in an intensive care unit (ICU): Psychiatric symptoms in healthcare professionals. Prog Neuropsychopharmacol Biol Psychiatry. 2021; 110: 110299, doi:10.1016/j .pnpbp.2021.110299. indexed in Pubmed: 33716042.
- Wang X, Pan Z, Cheng Z. Association between 2019-nCoV transmission and N95 respirator use. J Hosp Infect. 2020; 105(1): 104-105, doi: 10.1016^^.2020.02.021, indexed in Pubmed: 32142885.
- Barycka K, Szarpak L, Filipiak KJ, et al. Comparative effectiveness of N95 respirators and surgical/face masks in preventing airborne infections in the era of SARS-CoV2 pandemic: A meta-analysis of randomized trials. PLoS One. 2020; 15(12): e0242901, doi: 10.1371/journal.pone.0242901. indexed in Pubmed: 33320847.
- Szarpak L, Smereka J, Filipiak KJ, et al. Cloth masks versus medical masks for COVID-19 protection. Cardiol J. 2020; 27(2): 218-219, doi: 10.5603/CJ.a2020.0054 indexed in Pubmed: 32285928.
- Saban M, Shachar T. The silent effect of COVID-19 on emergency departments: How to avoid complacency? Disaster Emerg Med J. 2020; 5: 224-226, doi: 10.5603/demj .a2020.0035.
- Alfano V, Ercolano S. The efficacy of lockdown against COVID-19: a cross-country panel analysis. Appl Health Econ Health Policy. 2020; 18(4): 509-517, doi: 10.1007/s40258-020-00596-3. indexed in Pubmed: 32495067.
- Gibson PG, Qin L, Puah SH. COVID-19 acute respiratory distress syndrome (ARDS): clinical features and differences from typical pre-COVID-19 ARDS. Med J Aust.2020; 213(2): 54-56.e1, doi: 10.5694 2.50674, indexed in Pubmed: 32572965.
- Ruetzler K, Szarpak L, Filipiak K, et al. The COVID-19 pandemic — a view of the current state of the problem. Disaster Emerg Med J. 2020; 5: 106-107, doi: 10.5603/demj .a2020.0015.
- Nurminen V, Seuter S, Carlberg C. Primary vitamin D target genes of human monocytes. Front Physiol. 2019; 10, doi: 10.3389/fphys.2019.00194.
- Medrano M, Carrillo-Cruz E, Montero I, et al. Vitamin D: effect on haematopoiesis and immune system and clinical applications. Int J Mol Sci. 2018; 19(9), doi: 10.3390/ijms19092663, indexed in Pubmed: 30205552.
- Szarpak L, Rafique Z, Gasecka A, et al. A systematic review and meta-analysis of effect of vitamin D levels on the incidence of COVID-19. Cardiol J. 2021; 28(5): 647654, doi: 10.5603/CJ.a2021.0072 indexed in Pubmed: 34308537.
- Rehan VK, Torday JS, Peleg S, et al. 1Alpha,25-dihydroxy-3-epi-vitamin D3, a natural metabolite of 1alpha,25-dihydroxy vitamin D3: production and biological activity studies in pulmonary alveolar type II cells. Mol Genet Metab. 2002; 76(1): 46-56, doi: 10.1016/s1096-7192(02)00022-7 indexed in Pubmed: 12175780.
- Quesada-Gomez JM, Entrenas-Castillo M, Bouillon R. Vitamin D receptor stimulation to reduce acute respiratory distress syndrome (ARDS) in patients with coronavirus SARS-CoV-2 infections: Revised Ms SBMB 2020_166. J Steroid Biochem Mol Biol. 2020; 202: 105719, doi: 10.1016/j.jsbmb.2020.105719 indexed in Pubmed:32535032.
- Page M, McKenzie J, Bossuyt P, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021: n71, doi: 10.1136/bmj.n71.
- Hozo SP, Djulbegovic B, Hozo I. Estimating the mean and variance from the median, range, and the size of a sample. BMC Med Res Methodol. 2005; 5: 13, doi: 10.1186/1471-2288-5-13, indexed in Pubmed: 15840177.
- Cochrane. Cochrane Handbook for Systematic Reviews of Interventions; 2019. www.training.cochrane.org/handbook (Access: 1 July 2019).
- Castillo ME, Costa LE, Barrios JV, et al. “Effect of calcifediol treatment and best available therapy versus best available therapy on intensive care unit admission and mortality among patients hospitalized for COVID-19: A pilot randomized clinical study”. J Steroid Biochem Mol Biol. 2020; 203: 105751, doi: 10.1016/i.j sbmb.2020.105751.
- Murai I, Fernandes A, Sales L, et al. Effect of vitamin D3 supplementation vs placebo on hospital length of stay in patients with severe COVID-19: a multicenter, doubleblind, randomized controlled trial. medRxiv. 2021, doi: 10.1101/2020.11.16.20232397.
- - - - - - Start of studies in this meta-analysis - - - - - -
- Alcala-Diaz JF, Limia-Perez L, Gomez-Huelgas R, et al. Calcifediol treatment and hospital mortality due to COVID-19: a cohort study. Nutrients. 2021; 13(6), doi: 10.3390/nu13061760. indexed in Pubmed: 34064175.
- Annweiler G, Corvaisier M, Gautier J, et al. Vitamin D supplementation associated to better survival in hospitalized frail elderly COVID-19 patients: the GERIA-COVID quasi-experimental study. Nutrients. 2020; 12(11): 3377, doi: 10.3390/nu12113377, indexed in Pubmed: 33147894.
- Cereda E, Bogliolo L, Lobascio F, et al. Vitamin D supplementation and outcomes in coronavirus disease 2019 (COVID-19) patients from the outbreak area of Lombardy, Italy. Nutrition. 2021; 82: 111055, doi: 10.1016/j.nut.2020.111055 indexed in Pubmed: 33288411.
- Hernández JL, Nan D, Fernandez-Ayala M, et al. Vitamin D Status in Hospitalized Patients with SARS-CoV-2 Infection. J Clin Endocrinol Metab. 2021; 106(3): e1343- e1353, doi: 10.1210/clinem/dgaa733. indexed in Pubmed: 33159440.
- Nogues X, Ovejero D, Pineda-Moncusí M, et al. Calcifediol treatment and COVID- 19-related outcomes. J Clin Endocrinol Metab. 2021; 106(10): e4017-e4027, doi: 10.1210/clinem/dgab405. indexed in Pubmed: 34097036.
- Tan CW, Ho LP, Kalimuddin S, et al. Cohort study to evaluate the effect of vitamin D, magnesium, and vitamin B in combination on progression to severe outcomes in older patients with coronavirus (COVID-19). Nutrition. 2020; 79-80: 111017, doi: 10.1016/j .nut.2020.111017 indexed in Pubmed: 33039952.
- - - - - End of studies in this meta-analysi - - - - -
- Xing K, Tu XY, Liu M, et al. Efficacy and safety of COVID-19 vaccines: a systematic review. Zhongguo Dang Dai Er Ke Za Zhi. 2021; 23(3): 221-228, indexed in Pubmed: 33691913.
- Callaway E. Delta coronavirus variant: scientists brace for impact. Nature. 2021; 595(7865): 17-18, doi: 10.1038/d41586-021-01696-3 indexed in Pubmed: 34158664.
- Li R, Rivers C, Tan Qi, et al. The demand for inpatient and ICU beds for COVID-19 in the US: lessons from Chinese cities. medRxiv. 2020, doi: 10.1101/2020.03.09.20033241 indexed in Pubmed: 32511447.
- The Lancet Rheumatology.Too long to wait: the impact of COVID-19 on elective surgery. Lancet Rheumatol. 2021; 3(2): e83, doi: 10.1016/s2665-9913(21)00001-1.
- Schwartz RA, Suskind RM. Azithromycin and COVID-19: Prompt early use at first signs of this infection in adults and children, an approach worthy of consideration. Dermatol Ther. 2020; 33(4): e13785, doi: 10.1111/dth.13785, indexed in Pubmed: 32510734.
- Borba MG, Val FF, Sampaio VS, et al. Effect of high vs low doses of chloroquine diphosphate as adjunctive therapy for patients hospitalized with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection: a randomized clinical trial. JAMA Netw Open. 2020; 3(4): e208857, doi: 10.1001/jamanetworkopen.2020.8857. indexed in Pubmed: 32330277.
- Kow CS, Hasan SS. Azithromycin in patients with COVID-19: Friend or foe? Clin Microbiol Infect. 2021; 27(1): 136-137, doi: 10.1016/j.cmi.2020.09.047 indexed in Pubmed: 33007473.
- Ho TC, Wang YH, Chen YL, et al. Chloroquine and hydroxychloroquine: efficacy in the treatment of the COVID-19. Pathogens. 2021; 10(2), doi: 10.3390/pathogens10020217. indexed in Pubmed: 33671315.
- Perveen RA, Nasir M, Talha KA, et al. Systematic review on current antiviral therapy in COVID-19 pandemic. Med J Malaysia. 2020; 75(6): 710-716, indexed in Pubmed: 33219182.
- Szarpak t, Dzieci?tkowski T, Jaguszewski MJ, et al. Is remdesivir important in clinical practice as a treatment of COVID-19? A study based on meta-analysis data. Pol Arch Intern Med. 2021; 131(1): 96-97, doi: 10.20452/pamw.15686, indexed in Pubmed: 33231938.
- Bradley R, Schloss J, Brown D, et al. The effects of vitamin D on acute viral respiratory infections: A rapid review. Adv Integr Med. 2020; 7(4): 192-202, doi: 10.1016/j .aimed.2020.07.011 indexed in Pubmed: 32837896.
- Town JA, Churpek MM, Yuen TC, et al. Relationship between ICU bed availability, ICU readmission, and cardiac arrest in the general wards. Crit Care Med. 2014; 42(9): 2037-2041, doi: 10.1097/CCM.0000000000000401 indexed in Pubmed: 24776607.
- Singh AK, Gupta R, Ghosh A, et al. Diabetes in COVID-19: Prevalence, pathophysiology, prognosis and practical considerations. Diabetes Metab Syndr. 2020; 14(4): 303-310, doi: 10.1016/j .dsx.2020.04.004 indexed in Pubmed: 32298981.
- Szarpak t, Nowak B, Kosior D, et al. Cytokines as predictors of COVID-19 severity: evidence from a meta-analysis. Pol Arch Intern Med. 2021; 131(1): 98-99, doi: 10.20452/pamw.15685, indexed in Pubmed: 33219785.
- Tang Lu, Yin Z, Hu Yu, et al. Controlling cytokine storm is vital in COVID-19. Front Immunol. 2020; 11: 570993, doi: 10.3389/fimmu.2020.570993. indexed in Pubmed: 33329533.
- Mata-Granados JM, Vargas-Vasserot J, Ferreiro-Vera C, et al. Evaluation of vitamin D endocrine system (VDES) status and response to treatment of patients in intensive care units (ICUs) using an on-line SPE-LC-MS/MS method. J Steroid Biochem Mol Biol. 2010; 121(1-2): 452-455, doi: 10.1016/i.isbmb.2010.03.078 indexed in Pubmed: 20399267.
- Dai Qi, Zhu X, Manson JE, et al. Magnesium status and supplementation influence vitamin D status and metabolism: results from a randomized trial. Am J Clin Nutr. 2018; 108(6): 1249-1258, doi: 10.1093/??274, indexed in Pubmed: 30541089.
- Sassi F, Tamone C, D'Amelio P. Vitamin D: nutrient, hormone, and immunomodulator. Nutrients. 2018; 10(11), doi: 10.3390/nu10111656 indexed in Pubmed: 30400332.
- Lurz E, Horne RG, Maattanen P, et al. Vitamin B12 deficiency alters the gut microbiota in a murine model of colitis. Front Nutr. 2020; 7: 83, doi: 10.3389/fnut.2020.00083. indexed in Pubmed: 32582756.
- Zheng D, Liwinski T, Elinav E. Interaction between microbiota and immunity in health and disease. Cell Res. 2020; 30(6): 492-506, doi: 10.1038/s41422-020-0332-7 indexed in Pubmed: 32433595.
- Annweiler C, Hanotte B, Grandin de l'Eprevier C, et al. Vitamin D and survival in COVID-19 patients: A quasi-experimental study. J Steroid Biochem Mol Biol. 2020; 204: 105771, doi: 10.1016/i.jsbmb.2020.10577L indexed in Pubmed: 33065275.
- Reijven PLM, Soeters PB, Reijven PLM, et al. Vitamin D: A magic bullet or a myth? Clin Nutr. 2020; 39(9): 2663-2674, doi: 10.1016/j .clnu.2019.12.028 indexed in Pubmed: 31959477.
- Murai IH, Fernandes AL, Sales LP, et al. Effect of a single high dose of vitamin D3 on hospital length of stay in patients with moderate to severe COVID-19: a randomized clinical trial. JAMA. 2021; 325(11): 1053-1060, doi: 10.1001/jama.2020.26848 indexed in Pubmed: 33595634.
- Jolliffe DA, Stefanidis C, Wang Z, et al. Vitamin d metabolism is dysregulated in asthma and chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2020; 202(3): 371-382, doi: 10.1164/rccm.201909-18670C, indexed in Pubmed: 32186892.
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